Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes
Patrick Han, Douglas Hanlon, Najla Arshad, Jung Seok Lee, Kazuki Tatsuno, Alp Yurter, Eve Robinson, Renata B. Filler, Olga Sobolev, Christine M. Cote, Félix Rivera-Molina, Derek Toomre, Tarek M. Fahmy, Richard L. Edelson
Abstract
Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs). Differentiation of monocytes into phDCs was concomitant with the formation of an "adhesion synapse," a biophysical junction enriched with platelet P-selectin and monocyte P-selectin glycoprotein ligand 1, followed by intracellular calcium fluxing and nuclear localization of nuclear factor κB. phDCs were more efficient than cytokine-derived DCs in generating tumor-specific T cell immunity. Our findings demonstrate that platelets mediate a cytokine-independent, physiologic maturation of DC and suggest a novel strategy for DC-based immunotherapies.